1. Field of the Invention
The present invention relates to novel perfluorochemicals, and to their synthesis by the method of direct liquid-phase fluorination with undiluted F.sub.2.
2. Description of the Prior Art
The use of perfluorochemical emulsions as blood substitutes has received intensive study since the pioneering experiments of Clark and Geyer. At this time, a commercially available perfluorochemical emulsion is being used in humans under limited official or government permission in the medical field in Japan and in the U.S.A.
An appropriate perfluorochemical for blood substitutes must be non-toxic and metabolically inert, must dissolve as much oxygen as possible, and must be eliminated from the body when it is no longer needed medically, preferably at least 90% within one month.
A major factor in elimination rate is vapor pressure, but vapor pressure is not the whole story, because it is reported that perfluoro-cis-decalin (b.p. 143.degree. C., vapor pressure at 37.degree. C.; 10.1 mmHg) has a slightly higher elimination rate than the trans isomer (b.p. 141.degree. C., vapor pressure at 37.degree. C.; 11.6 mmHg), though a slightly lower vapor pressure. Furthermore, it is found that the perfluorochemicals having hetero atoms, such as N and/or O, have much slower elimination rates that perfluoro hydrocarbon analogues of similar molecular weight, even if they have an appropriate vapor pressure. It is more likely that the elimination rate of perfluorochemicals, at least the C.sub.9 -C.sub.11 perfluorochemicals which are the most useful for blood substitutes, depends strongly on their chemical structure rather than boiling point and vapor pressure. For example, the elimination rate order in the following perfluorochemicals is IV&gt;&gt;III.gtoreq.I&gt;II, even though their vapor pressures and b.p.'s are in extremely narrow range.
__________________________________________________________________________ I II III IV __________________________________________________________________________ ##STR2## ##STR3## ##STR4## ##STR5## C.sub.10 F.sub.22 O (554) C.sub.10 F.sub.20 O (516) C.sub.10 F.sub.20 (500) C.sub.10 F.sub.18 (462) b.p. 136-137.degree. C. 144-145.degree. C. 144-145.degree. C. 141-142.degree. C. vapor pressure at 37.degree. C.: 11.8 mmHG 11.7 mmHg 12.5 mmHg 12.7 mmHg __________________________________________________________________________
In formulae shown herein, "F-" means that the compound is perfluorinated, unless otherwise stated.
Nichka discloses in DT-OS 2253534 as the solvent of oxygen perfluoroisopropyl n-hexyl ether of the formula ##STR6##
Apparently the data so far obtained do not reveal the relationship between chemical structure and elimination rate, probably owing to the limited range of perfluorochemical structures so far tested.
The second point is the problem of toxicity which causes pulmony emphysema. Perfluorochemicals having a lower vapor pressure have generally this toxicity due to the fast elimination from the body through the lung. The elimination burdens the lung and causes the pulmonary emphysema.
The third point is stability of the emulsion of perfluorochemicals. The emulsion having particles of which size is less than 0.3.mu., preferably less than 0.2.mu. must be stable under sterilizing heat and also during long time storage.
The principle industrial processes now employed in perfluorochemical synthesis, namely electrochemical fluorination or cobalt trifluoride fluorination are not suitable for the fluorination of sensitive compounds, for example, highly branched compounds or structurally strained compounds, because considerable carbon-skeleton rearrangement and/or breakdown of the carbon skeleton often occurs during the reaction, resulting not in pure substances but mixtures of isomeric compounds containing impurities and incompletely fluorinated compounds. In addition to these principal routes to perfluorochemicals, one other is worth mentioning: The direct fluorination of solid starting materials using elemental F.sub.2 and a diluent such as N.sub.2 or He is very general and powerful laboratory synthesis of a wide variety of perfluorochemicals, including cyclic and branched hydrocarbons and ethers. Unfortunately, this method is impractical for commercial use. The inherently slow mass transfer through solids at low temperature makes it unlikely that the process can be economically scaled up, and even the published laboratory synthesis of low molecular weight products involves many days of reaction time to produce only a few grams of product.